We are developing tissue culture model systems to elucidate the biologic characteristics of early abnormal proliferations in urothelium obtained from patients by transurethral resection. Specimens from over 70 patients have been cultured in a three-dimensional matrix of collagen-coated cellulose sponge and a variety of morphologic changes have been identified after one week of cultivation. To increase the breadth of our ablity to subclassify lesions of similar histopathology, we have tried to cultivate clinical tumors in the meniscus-gradient model, where monolayers of bladder carcinoma cell lines have shown distinctive zonal responses to the gradient of decreasing oxygen tension. We are now combining collagen-coated cellulose sponge and meniscus gradient principles, and early work is very encouraging. As an additional tool for subclassification of clinical lesions we are developing a series of molecular probes using bladder cancer cell lines (Cancer Research, 35: 1873, 1975). BIBLIOGRAPHIC REFERENCES: Toyoshima, K. and Leighton, J.: Vitamin A Inhibition of Keratinization in Rat Urinary Bladder Cancer Cell Line Nara Bladder Tumor No. 2 in Meniscus Gradient Culture. Cancer Res. 35: 1873-1879, 1975. Toyoshima, K. and Leighton J.: Bladder Calculi and Urothelial Hyperplasia with Papillomatosis in the Rat Following Insertion of Chalk Power in the Bladder Cavity with Subsequent Trauma of the Bladder Wall. Cancer Res. 35: 3786-379l, 1975.